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Abstract

Kappa opioid receptor (KOPr) activation antagonizes many cocaine-related behaviors but adverse
side effects such as sedation, dysphoria and depression limit their therapeutic use. Recently,
salvinorin A (Sal A), a naturally occurring KOPr agonist, has been shown to attenuate cocaineinduced
drug-seeking in a model of relapse in rats. The present study evaluated the effects of acute
Sal A exposure on cocaine-induced hyperactivity and cocaine sensitization in rats. Acute treatment
with the dose of Sal A that decreased drug-seeking in a previous study (0.3 mg/kg), significantly
attenuated the expression of cocaine sensitization. This dose of Sal A failed to affect spontaneous
locomotion or to produce a conditioned taste aversion to a novel-tasting saccharin solution.
However, Sal A decreased climbing and swimming time and increased time spent immobile in the
forced swim test. These findings indicate that Sal A, just like traditional KOPr agonists, attenuates
cocaine-induced behavioral sensitization but does not produce the adverse effect of conditioned
aversion, suggesting improved potential compliance. However, pro-depressive effects were also
produced and these effects may limit the therapeutic potential.